It has been suggested that obesity rates around the world are at epidemic proportions. Relevant to this threat are the sequelae that are associated with obesity, such as increased risk of developing type 2 diabetes, heart disease, and stroke. With these statistics in mind, research into understanding the systems that are involved in regulating body weight and food intake-associated behaviors is critical. There is a notable gap in our understanding of "higher-order" cortical control of basic appetitive behaviors. To address this gap, we propose to explore the medial prefrontal cortex, an area rich in connections to 'downstream'regions that mediate homeostatic and hedonic control of feeding behavior. Particularly germane to this goal are preliminary results from our lab showing that stimulation of mu-opioid receptors in the mPFC augments food intake in both food- deprived and non-deprived animals, and promotes extreme hyperactivity and fragmentation of motor repetoires. Surprisingly, very little is known about the functional role of PFC opioids and very few studies have examined the behavioral effects following local PFC opioid manipulation. Thus, we propose to explore the neuropharmacology and anatomical substrates underlying these effects, and to investigate the precise behavioral constructs underlying our observed effects. PUBLIC HEALTH RELEVANCE: The work outlined in this proposal has the potential to enhance our understanding of how higher-order cognitive factors impinge upon, and perhaps organize and regulate, basic homeostatic mechanisms related to food intake. Hence, this work could lead to novel and exciting insights into the 'top-down'executive control of basic motivational and homeostatic processes. The proposed work may also elucidate important new knowledge regarding peptide control of prefrontal cortical function, which could have profound translational implications for disorders like ADHD and Schizophrenia.